This proposal is designed to determine the major regulatory mechanisms and localization of cytosolic phospholipase A2 gamma (cPLA2gamma). The enzyme is a newly discovered paralog of the group IV cytosolic phospholipase A2 family involved in signaling and inflammation in mammalian cells. Experiments proposed here are designed to define the localization of endogenous cPLA2gamma in human skeletal muscle cells. Unlike other PLA2s, cPLA2gamma is constitutively bound to the membrane and enriched in skeletal and cardiac muscle. Preliminary data indicates that cPLA2gamma is acylated and prenylated. The role of these modifications in membrane binding will be investigated. Experiments on cPLA2gamma-induced apoptosis in mammalian cells will also be carried out. Finally, we will determine whether cPLA2gamma is regulated by mechanism of regulation and localization of cPLA2gamma will lead to an understanding of the physiological functions of cPLA2gamma in human skeletal muscle cells,